The present invention relates generally to methods and devices for the quantitative determination of an analyte in a sample and, in particular, to methods for extending the quantitative measuring range of an analyte in a sample, and test devices employing same.
A widespread analytical method for the rapid determination of analytes such as, for example, drugs, pregnancy hormones, infectious diseases or cardiac markers utilizes immunological test strips. In this connection qualitative tests that are read purely visually (e.g., Roche CARDIAC® D-dimer, Trop T sensitive, etc.) as well as quantitative tests that are evaluated by means of a reading device (e.g., Elecsys® proBNP, Roche CARDIAC® proBNP, etc.) are widely used.
Such quantitative immunological test strips are characterized in particular by their easy handling. The test strips are usually based on the fact that the test strip contains a reagent which leads to a detectable signal by reaction with the analyte in the sample. The detectable signal is usually determined by reflectance measurement after a specified time period. The time period between contacting the analyte and reagent and measuring the signal is chosen to be as long as possible. This ensures a long reaction time between the reagent and analyte and thus ensures the highest possible sensitivity of such test strips. However, for reasons of reaction kinetics it is no longer possible after such a long reaction period to quantitatively determine analytes which are present in a high concentration in a sample.
Hence, such test strips still have considerable weaknesses with regard to their performance compared to conventional laboratory analytical systems such as, e.g., Elecsys® (Roche Diagnostics), IM (Abbott), Dimension® (Dade Behring). Especially the measuring accuracy and the dynamic measuring range are considerably impaired in test strips for example in comparison to reactions involution. This limits their use when determining analytes which require a high sensitivity as well as the measuring range as large as possible. In particular, for the emergency care of patients it would be very helpful for the attending physician if a test or a method could be provided which, due to its high sensitivity, could, on the one hand, enable certain diseases to be reliably excluded but, on the other hand, would also provide a large measuring range. A large measuring range for an analyte is particularly desirable for risk stratification and for therapeutic monitoring. A measuring range extension of tests would be particularly desirable for those pathological conditions in which the concentration of an analyte or marker that is characteristic for the condition correlates with the severity of the pathological condition. An elevated marker concentration (e.g., NT-proBNP) can in such eases indicate an increased risk situation for a patient.